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Volumn 130, Issue 12, 2008, Pages 4153-4157

Powdered KOH in OMSO: An efficient base for asymmetric cyclization via memory of chirality at ambient temperature

Author keywords

[No Author keywords available]

Indexed keywords

CHIRAL ENOLATE INTERMEDIATES; POTASSIUM HEXAMETHYL-DISILAZIDE;

EID: 41149135353     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja077684w     Document Type: Article
Times cited : (79)

References (48)
  • 3
    • 0042929265 scopus 로고    scopus 로고
    • For reviews on memory of chirality, see a
    • For reviews on memory of chirality, see (a) Kawabata, T.; Fuji, K. Top. Stereochem. 2003, 23, 175-205.
    • (2003) Top. Stereochem , vol.23 , pp. 175-205
    • Kawabata, T.1    Fuji, K.2
  • 20
    • 0010095120 scopus 로고
    • For reviews of stereoselective C-C bond formation based on enolate chemistry, see (a) Morrison, J. D. Ed, Academic Press, Inc, New York
    • For reviews of stereoselective C-C bond formation based on enolate chemistry, see (a) Morrison, J. D. Ed. Asymmetric Synthesis; Academic Press, Inc.: New York, 1984; Vol.3, pp 1-341.
    • (1984) Asymmetric Synthesis , vol.3 , pp. 1-341
  • 25
    • 41149142181 scopus 로고    scopus 로고
    • The racemization barrier at 20°C was roughly estimated from that at -78 °C based on the assumption that ΔS‡ of the unimolecular racemization process (bond rotation along the chiral C-N axis) is nearly zero.
    • The racemization barrier at 20°C was roughly estimated from that at -78 °C based on the assumption that ΔS‡ of the unimolecular racemization process (bond rotation along the chiral C-N axis) is nearly zero.
  • 30
    • 0034712270 scopus 로고    scopus 로고
    • For recent reviews on the importance and preparation of cyclic amino acids with a tetrasubstituted stereocenter, see (a) Cativiela, C, Díaz-de-Villegas, M. D. Tetrahedron: Asymmetry 2000, 11, 645-732
    • For recent reviews on the importance and preparation of cyclic amino acids with a tetrasubstituted stereocenter, see (a) Cativiela, C.; Díaz-de-Villegas, M. D. Tetrahedron: Asymmetry 2000, 11, 645-732.
  • 33
    • 41149120896 scopus 로고    scopus 로고
    • Commercial (not dry) DMSO was used without further purification
    • Commercial (not dry) DMSO was used without further purification.
  • 34
    • 41149150588 scopus 로고    scopus 로고
    • One might suppose that the active base in these reactions is a dimsyl anion generated in a small quantity from KOH and DMSO pKa's of H2O and DMSO in DMSO are 31 and 35, respectively; ref 7, However, this seems not feasible because the dimsyl anion prepared from KH in DMSO showed a different reactivity in the reaction of 1. Treatment of 1 with 3.0 mol equiv of potassium dimsylate in DMSO at 20°C for 2 h gave 2 in 99% ee and 68% yield together with the corresponding carboxylic acid of 2 in 25% yield
    • 2O and DMSO in DMSO are 31 and 35, respectively; ref 7). However, this seems not feasible because the dimsyl anion prepared from KH in DMSO showed a different reactivity in the reaction of 1. Treatment of 1 with 3.0 mol equiv of potassium dimsylate in DMSO at 20°C for 2 h gave 2 in 99% ee and 68% yield together with the corresponding carboxylic acid of 2 in 25% yield.
  • 35
    • 41149134172 scopus 로고    scopus 로고
    • Whereas determination of the racemization barrier of the enolate generated from 28 with KOH/DMSO is desirable, it was not possible. This is because (1) KOH/DMSO cannot be used at low temperatures suitable for the measurement of enolate racemization, and (2) KOH/DMSO cannot generate the enolate from 28 in a quantitative manner. Quantitative generation of the enolate in a much shorter period than the half-life of racemization of the enolate is indispensable for the measurement of the racemization barrier.
    • Whereas determination of the racemization barrier of the enolate generated from 28 with KOH/DMSO is desirable, it was not possible. This is because (1) KOH/DMSO cannot be used at low temperatures suitable for the measurement of enolate racemization, and (2) KOH/DMSO cannot generate the enolate from 28 in a quantitative manner. Quantitative generation of the enolate in a much shorter period than the half-life of racemization of the enolate is indispensable for the measurement of the racemization barrier.
  • 36
    • 84987564680 scopus 로고    scopus 로고
    • Amine-free lithium enolates have been known to be more reactive than the enolates in the presence of a secondary amine generated in situ by abstraction of the α proton of the carbonyl group with the lithium amide base; see (a) Laube, T, Dunitz, J. D, Seebach, D. Helv. Chim. Acta. 1985, 68, 1373-1393
    • Amine-free lithium enolates have been known to be more reactive than the enolates in the presence of a secondary amine generated in situ by abstraction of the α proton of the carbonyl group with the lithium amide base; see (a) Laube, T.; Dunitz, J. D.; Seebach, D. Helv. Chim. Acta. 1985, 68, 1373-1393.
  • 39
    • 41149160571 scopus 로고    scopus 로고
    • We suppose that a water molecule generated by deprotonation of the substrate with KOH may be excluded from the coordination sphere of the potassium enolate by strongly coordinating DMSO molecules
    • We suppose that a water molecule generated by deprotonation of the substrate with KOH may be excluded from the coordination sphere of the potassium enolate by strongly coordinating DMSO molecules.
  • 40
    • 41149162462 scopus 로고    scopus 로고
    • 50/100 was roughly estimated to be 0.02 sec at 20°C based on the racemization barrier of C (15.5 kcal/mol).
    • 50/100 was roughly estimated to be 0.02 sec at 20°C based on the racemization barrier of C (15.5 kcal/mol).
  • 41
    • 41149112249 scopus 로고    scopus 로고
    • For an additional example, seven-membered cyclization of a substrate derived from L-phenylalanine gave the product in 49% ee (25% yield) by treatment with powdered KOH in dry DMSO at 20°C for 2 h.
    • For an additional example, seven-membered cyclization of a substrate derived from L-phenylalanine gave the product in 49% ee (25% yield) by treatment with powdered KOH in dry DMSO at 20°C for 2 h.
  • 42
    • 41149146870 scopus 로고    scopus 로고
    • The rates of enolate formation from the substrates undergoing four-membered cyclization are assumed faster than those undergoing six-membered cyclization. Reasons are totally unclear. A possible explanation might be due to the slight increase in the acidity of α proton in the former substrates caused by the inductive effect of the bromo group at the N-2-bromoethyl substituent or due to the favorable delivery of OH- via chelation of K+ with the bromo group
    • + with the bromo group.


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